The Gulf Long-term Follow-up Study (GuLF STUDY, www.gulfstudy.nih.gov) was initiated in response to the April 2010 explosion of the Deepwater Horizon (DWH) drilling rig and resulting oil spill in the Gulf of Mexico, the largest marine oil spill in U.S. history. NIEHS is carrying out a long-term study looking at the potential acute and chronic health effects of this disaster in various responder populations. Building upon telephone and in-person data collection efforts that began in 2011, NIEHS has amassed an invaluable amount of longitudinal questionnaire data on 32,608 individuals who completed a telephone enrollment questionnaire between 2011-2013. During this time, a smaller subset participated in a home visit to provide additional questionnaire as well as anthropometric, physiologic, and biospecimen data (n=11,193). These data are being used to explore a variety of different outcomes stemming from this historic disaster including respiratory, cardiovascular, dermatologic, mental health, neurological, hepatic, renal, endocrine, hematological, and other systemic effects. Follow-up data were collected on 21,256 participants between 2013-2016. With financial support from SAMHSA, additional information was collected on mental health trajectories for a subset of 2,859 individuals between 2013-2016. Of these individuals, 1,506 completed all 4 repeated data collection opportunities. A subset of 3,403 participants completed a more comprehensive clinical exam (2014-2016). The clinic exam included additional measures of lung function, standardized measures of neurological function, questionnaires, and biological sample collection. All participants, regardless of active participation in follow up interviews or exam, are followed over time via linkage to cancer and mortality records. Participants will be followed for 10 or more years. Starting in 2013, contact information is updated annually, usually in connection with Newsletter mailings. The first cohort-wide (except for Vietnamese-speaking participants) follow-up interview was completed in May 2016. The interview assessed changes in health status and factors that could confound associations between exposures and outcomes. A second follow-up interview began in 2018. In addition to updating previously collected questionnaire data, the new interview adds questions about fertility and reproductive health. There are also new questions on sleep, metabolic health, and social factors to enable studies of health disparities. As part of this interview, we validate self-reported health endpoints through questions on medications or treatments that support the diagnosis (e.g. use of insulin or oral agents by diabetics), and requesting medical record release authorization for selected conditions. One unique aspect of this work, in addition to the magnitude of the spill and the size of the cohort relative to other oil spill cohorts, is our extraordinary effort to characterize exposures. We used questionnaires and measurement data to develop an ordinal job-exposure matrix (JEM) for airborne THC as a composite marker for oil spill exposures. We also developed ordinal measures for exposure to dispersants and particulates from burning oil using questionnaires and external information we gathered about OSRC activities and requirements. Despite the large number of measurements, the exposures for most individuals in the GuLF STUDY were not directly measured. Thus, we used questionnaire data to identify groups of jobs/tasks with likely similar exposures and used the measurement data to characterize the exposures in those jobs. Exposures were found to vary by location, task, and time in relation to the capping of the well, among other factors. Methods were developed and/or evaluated to identify the least biased way to deal with values below the LOD and other censoring. The development of quantitative exposure measures is nearly complete. These measures incorporate time spent in various jobs/tasks and additional information from measurements made during the spill and industry and government documentation of cleanup activities. Metrics will soon be available for individual BTEX chemicals as well as total hydrocarbons, PM2.5, dispersants, and other chemicals. A measure of dermal exposure to oil has also been completed. A paper describing the creation of the ordinal job-exposure matrix used for the exposure assessment has been published and will be followed by a monograph of the methods used to create the comprehensive exposure assessment. Ongoing analysis of baseline and follow-up data continues to be focused on mental health, pulmonary function, cardiovascular outcomes, respiratory health and a range of specific and non-specific symptoms reported by participants while working on the response and clean-up. We evaluated predictors of depression and PTSD in the study population (Kwok et al. 2017). Overall, workers had more depression (PR 1.22, 95% CI 1.08. 1.37) and PTSD (PR 1.35, 1.07, 1.71) than nonworkers. Among workers, those who had who had potentially stressful experiences like smelling the oil, dispersants, or cleaning chemicals had elevated prevalence of depression as did those who reported having to stop work because of the heat or being a commercial fisherman who could not work at their regular job during the spill. A recent analysis showed that mental health symptoms were increased with increasing number of disaster experiences, with greater levels of depression and PTSD-like symptoms among persons who experienced both disruption due to Hurricane Katrina and worked on oil spill clean-up (Manuscript under revision). Pulmonary function testing was done during the GuLF STUDY home exams. Workers who performed decontamination tasks and those with high exposure to burning oil/gas had reduced lung function as measured by FEV1, FVC, and the FEV1/FVC ratio (Gam et al. 2018). In addition, workers handling oily wildlife (plants, birds, dead animal) had significantly reduced lung function (Gam et al., in press). Total hydrocarbon exposure was, however, not related to measured pulmonary function (Gam et al. 2018). Several analyses considered risk of MI in relation to various oil spill exposures. Risk for incident nonfatal MI was suggestively increased among those who cleaned up after the oil spill (Strelitz et al., 2018). Total MI (fatal and nonfatal) over 5 years of follow-up was also shown to be associated with higher levels of exposure to hydrocarbons (Strelitz et al., in revision). Although not an oil spill chemical per se, blood levels of styrene were found to be higher among gulf coast residents participating in this study compared to levels from a U.S. population sample (NHANES)(Werder, et al. 2017). Styrene, at occupational exposure levels, is a neurotoxin. We investigated the potential link between population level styrene exposures and neurological symptoms and function. Two exposure measures were used - blood levels of styrene and ambient exposures as estimated using an EPA national air toxics database linked to the residences of GuLF STUDY participants. Styrene was associated with both symptoms and tests of neurological function (Werder et al., 2018; Werder et al. in revision). Other recent papers from the study describe symptoms associated with potential exposure to dispersants and changes in hematologic measures associated with BTEX exposures. Ongoing and future work will evaluate associations with chemical-specific quantitative exposure measures and consider changes in symptoms and clinical measures over time.